UNIT DRUG TOXICITY& TOLERANCE

DISCUSSION POINTS

1. Read the quote. Do you agree or disagree with the author’s message.

The need for general scientific understanding by the public has never been larger, and the
penalty for scientific illiteracy never harsher… Lack of scientific fundamentals causes
people to make foolish decisions about issues such as the toxicity of chemicals, the efficacy
of medicines, the changes in the global climate.

(Peter Agre)
2. Examine the diagram below. Dicuss about Drug Tolerance

overdose toxicity
antidote

bloodstream

antidote DRUG TOXICITY

symptoms
poisoning
anaphylaxis treatment

Vocabulary
Iatrogenic /aɪˌætrəʊˈdʒɛnɪk/- induced in a patient as the result of a physician's words or actions,
esp as a consequence of taking a drug prescribed by the physician.
Anaphylaxisˌ/ænəfɪˈlæksɪs/- extreme sensitivity to an injected antigen, esp.
a protein, following a previous injection.
Idiosyncrasy /ɪdioʊsɪŋkrəsi/- an abnormal reaction of an individual to specific foods, drugs, or
other agents.
Pharmacotherapy/fɑːməkəˈθɛrəpɪ/- the healing and cure of illness by the administration of drugs.
 DRUG TOXICITY
Toxicity refers to how poisonous or harmful a substance can be. Toxicity is the degree to which
a chemical substance or a particular mixture of substances can damage an organism. In the context
of pharmacology, toxicity occurs when a person has accumulated too much of a drug in his
bloodstream, leading to adverse effects within the body. Drug toxicity is the critical or lethal
reaction to an erroneous dosage of a medication. Drug toxicity may occur when the dose is given is
too high or the liver or kidneys are unable to remove the drug from the bloodstream, allowing it to
accumulate in the body.The effects of the medication are more pronounced at toxic levels, and side
effects may be severe. The reasons for toxicity vary depending on the mixture of drugs. Toxicity
may result when the dose is too high, or it may result when the liver or kidneys are unable to
remove the drug from the bloodstream. Many commonly prescribed medications can accumulate in
the bloodstream and result in toxicity. Symptoms of drug toxicity depend on the drug taken.
Treatment for drug toxicity also depends on the drug taken and the blood level of the drug. There
are several ways in which drug toxicity may be treated. If the toxicity is the result of an
acute overdose, then a person may undergo stomach pumping to remove drugs that have not yet
been absorbed. Activated charcoal may be given to bind the drugs and prevent them from being
absorbed into the blood (instead, it is eliminated from the body through stool). Other medications
may also be given as an antidote. All drugs have primary intended effects and secondary unintended
effects, the latter known as side effects or adverse effects. Although side effects can be neutral or
even beneficial, side effects are typically undesirable. Adverse effects can range in severity from
nuisance to life threatening. These effects make many patients unwilling to take drugs on a regular
basis, and this lack of compliance represents a major practical limitation of pharmacotherapy. Drug
toxicity, also called adverse drug reaction or adverse drug event, is defined as the "manifestations of
the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques.
It does not include accidental or intentional poisoning..." The meaning of this expression differs
from the meaning of "side effect", as this last expression might also imply that the effects can be
beneficial. Drug toxicity takes place when a person accumulate too much of a drug in blood, which
may leads to adverse effects on the body. This may also occur when the dose of a drug is too high
which are unable to remove the drug from the blood. Drug toxicity may occur a result of over dose
of a medication which have too much of a drug in a persons system at once. This may happen when
the dose taken exceeds the prescribed dose, either accidentally and intentionally. Drug toxicity can
occur as a result of the over-ingestion of a medication—having too much of a drug in a person's
system at once. This can happen if the dose taken exceeds the prescribed dose, either intentionally
or accidentally. A person with drug toxicity has accumulated too much of a medication in the
bloodstream. The effects of the medication are more pronounced at toxic levels, and side effects
may be severe. Toxicity may result when the dose is too high, or it may result when the liver or
kidneys are unable to remove the drug from the bloodstream. Many commonly prescribed
medications can accumulate in the bloodstream and result in toxicity. Symptoms and treatment of
drug toxicity depends on the drug taken. Drug toxicity is an unpleasant and potentially dangerous
effect of a drug. Idiosyncrasy is an example of an unpredictable type of drug toxicity. This is any
unexpected and uncommon side effect that develops after administration of a drug. For example, in
some people, penicillin causes an idiosyncratic reaction, such as anaphylaxis. Anaphylaxis occurs
as a result of exposure to a previously encountered drug or foreign substance (antigen). Other types
of drug toxicity are more predictable and expected, such as stomach upset after aspirin use.
Physicians are trained to be aware of the potential toxic effects of all drugs that they prescribe.
Iatrogenic disorders can occur, however, as a result of mistakes in drug use or because of individual
sensitivity to a given agent.
3. Answer the questions from the comprehension guide

What is drug
toxicity?

Why may
When may STEROIDS activated
drug toxicity charcoal be
occur? given?

What do
symptoms of
drug toxicity
depend on?

4. Fill in the gaps with words formed from those in paranthesis

After laboratory ___________(to screen), firms conduct clinical investigations, or "trials," of

the drug on human patients. Human clinical trials normally take place in three phases. First,
___________(medicine) scientists administer the drug to a small group of _________(health)
volunteers in order to determine and adjust dosage levels, and monitor for side effects. If a
drug ________(to appear) useful and safe, ____________(to add) tests are conducted in two
more phases, each phase using a _____________(succession) larger group of volunteers or
carefully ____________(to select) patients. Once a drug has successfully passed animal and
clinical tests, the Food and Drug Administration (FDA) must review the drug’s
__________(to perform) on human patients, the results of which carefully __________(to
document), before approving the substance for commercial use. The entire process, from the
first __________(to discover) of a promising new compound to FDA approval, can take up to
15 years, but scientific and __________(to inform) technology advances will shorten that
process considerably for many drugs. After FDA approval, problems of production methods
and costs must be ___________(to work) out before manufacturing begins.

5. Fill in the blanks with the appropriate words from the box.

Toxicology, response, properties, to cause, exposure, poison, implies,

dosing, environment, doses, toxic to achieve, substances, exposures, events.
Pharmacology deals with drugs and their chemical _____________or characteristics, their
mode of action, the physiological ___________to drugs, and the clinical uses of drugs.
Pharmacology intersects with toxicology when the physiological response to a drug is
an adverse effect. ____________is often regarded as the science of poisons or poisoning, but
developing a strict definition for poison is problematic. A ___________ is any substance,
including any drug, that has the capacity to harm a living organism.
However, poisoning inherently ___________that damaging physiological effects result from
__________to pharmaceuticals, illicit drugs, or chemicals. So each drug in the pharmacopeia
is a potential poison, and individual dose, situation, ___________, and gene-related factors
contribute to a drug's ability ____________its adverse potential. Some chemicals may
inherently be poisons, which has no known necessary physiological role in the human body,
and which is known ____________neuronal injury even at very low exposure levels. Most
pharmaceuticals are threshold poisons; at therapeutic ____________the drug is used to confer
a health advantage, but at higher ___________the drug may produce a toxic effect. The
preclinical toxicity testing on various biological systems reveals the species, organ and dose-
specific ________effects of an investigational product. The toxicity of ___________can be
observed by studying the accidental ___________to a substance in vitro studies using cells/
cell lines in vivo exposure on experimental animals. Toxicity tests are mostly used to examine
specific adverse ___________or specific end points such as cancer, cardiotoxicity and
skin/eye irritation.

References

https://yandex.ru/images/search?text=DRUG%20TOXICITY%20quote&stype=image&lr=10313&sourc
e=wiz
https://quotes.yourdictionary.com/toxicity
https://www.verywellmind.com/toxicity-meaning-and-signs-and-symptoms-1067226
https://en.wikipedia.org/wiki/Toxicity
http://accessmedicine.mhmedical.com/content.aspx?bookid=1613&sectionid=102157436
https://www.britannica.com/science/drug-chemical-agent/Types-of-drugs
https://pixabay.com/images/search/antibiotics/
https://yandex.ru/images/search?text=Drugs%20toxicity&from=tabbar&pos=4&img_url=https%3A%
2F%2Fis4-
ssl.mzstatic.com%2Fimage%2Fthumb%2FPurple122%2Fv4%2F86%2F06%2F53%2F8606534a-e202-
e358-82a4-ed95261cbc1d%2Fsource%2F512x512bb.jpg&rpt=simage
 DRUG TOLERANCE

DISCUSSION POINTS

1. Examine the diagram below. Dicuss about Drug Tolerance

behavioral
abused drug tolerance
dependence

pharmacodynamic
tolerance

physical DRUG TOLERANCE

phenomenon

tolerance
drug
tolerability
pharmacokinetic drug
tolerance sensitization

Vocabulary
Tolerance /tɒlərəns/- diminishing effect of a drug resulting from repeated administration at a given dose.
Drug tolerance- a pharmacological concept describing subjects' reduced reaction to a drug following its
repeated use.
Drug tolerability--the degree to which overt adverse effects of a drug can be tolerated by a patient.
Drug sensitizationˌ/sensɪtəˈzeiʃən/ or reverse tolerance – the escalating effect of a drug resulting from
repeated administration at a given dose.
Pharmacodynamic tolerance - a type of drug tolerance wherein the chemistry of the brain comes to be
acclimated to the existence of the drug, that in turn then loses its ability for changing brain activity.
Addiction – a biopsychosocial disorder characterized by compulsively seeking to achieve a desired
effect, such as intoxication, despite harm and adverse consequences to self and others.
Addictive behavior – a behavior that is both rewarding and reinforcing
Addictive drug – a drug that is both rewarding and reinforcing.
Dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated
exposure to a stimulus.
Drug withdrawal – symptoms that occur upon cessation of repeated drug use.
Physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms.
Psychological dependence – dependence that involves emotional–motivational withdrawal symptoms.
Behavioral tolerance--drug's decreased potency in affecting a specified behavior after repeated or
continuous exposure to the drug.
 READING & WRITING
DRUG TOLERANCE

The phenomenon of tolerance emerges as one of the chief characteristics in the physiological and
psychological make-up of every abuser, addict, or chemically dependent person. Tolerance refers to
the process by which the body acclimates to the presence of an abused drug. Drug tolerance is
a pharmacological concept describing subjects' reduced reaction to a drug following its repeated use.
Increasing its dosage may improve the drug's effects; however, this may accelerate tolerance, further
reducing the drug's effects. Drug tolerance is indicative of drug use but is not necessarily associated
with drug dependence or addiction. Adaptive changes occur in response to the repeated exposure to a
particular drug, the result is usually a loss of sensitivity to the drug. This decreased response is
tolerance.
Professionals say the drug tolerance definition is as a state of progressively decreased responsiveness
to a drug. Consequently, a larger dose of the drug is necessary to achieve the effect originally obtained
by a smaller dose. The drug tolerance definition refers to the body’s ability governed by genetic factors
and adaptive changes by the body and it includes various symptoms. Some of the more common
features of tolerance include: irreversibility, meaning that once this psychic damage develops there is
no known remedy that will enable the addict to revert back to a time before the establishment of
tolerance.
The opposite concept to drug tolerance is drug reverse tolerance (or drug sensitization), in this case
subject's reaction or effect will increase following its repeated use. The two notions are not
incompatible and tolerance may sometimes lead to reverse tolerance. For example, heavy drinkers
initially develop tolerance to alcohol (requiring them to drink larger amounts to achieve a similar
effect) but excessive drinking can cause liver damage, which then puts them at risk of intoxication
when drinking even very small amounts of alcohol.
Drug tolerance should not be confused with drug tolerability, which refers to the degree to which
overt adverse effects of a drug can be tolerated by a patient. Tolerance occurs along the entire
spectrum of abuse of some medication prolonged consumption, be it sedative, stimulant and painkiller,
tolerance can manifest via several routes, which means it can develop regardless of whether the person
is injecting, or smoking their drugs. Complicating matters is the fact that physiological tolerance,
which invariably develops in tandem with psychological dependence, frequently manifests as
secondary mental health disorders such as depression, anxiety, or some form of mood disorder.
 Remember, it is common for people to develop a tolerance to their pain medication and to need
higher doses to achieve the same level of pain relief. Such a situation is normal and is not a sign of
addiction. Symptoms of drug withdrawal tend to be the opposite of the effects of the drug. If the effect
of the drug is sedation, the withdrawal effect will likely be hyper-excitability. If the effect was
stimulation the withdrawal effect will likely be emotional depression.
 Physiological tolerance also occurs when an organism builds up a resistance to the effects of a
substance after repeated exposure. Ironically this can occur with environmental substances, such as salt
or pesticides.
It should be noted again that drugs designed to treat chronic pain are highly addictive, and that there is
a very real ratio between the painkiller’s effectiveness controlling pain and the intensity of the
euphoria that is generated. Any analgesic or sedative will be proportionately as addictive as it is
effective. Opiates, which are the most common drugs doctors prescribe to treat pain, generate effects
similar to those of opium or morphine and are highly addictive. These drugs include: hydrocodone,
vicodin, morphine, oxycodone, meperidine. A fair question is who is at risk to develop tolerance. Most
individuals who take pain medications in the manner consistent with what the physician orders do not
become addicted to drugs nor do they exhibit tolerance (it does, however, happen from time to time).
This scenario changes when dealing with someone for whom addiction is part of their history. People
previously addicted to some medication in the past, or those with a family history of addiction to drugs
or alcohol may be at increased risk of becoming addicted to narcotics.
2. Agree or disagree with the following statements, give arguments to support your
opinion.

1. Tolerance can happen if you’ve been using a medication or other drug for a while. Don’t
suddenly stop taking the drug. There are steps your doctor can take to manage drug tolerance
and help you feel better. Some medications and conditions with reports of tolerance include:
anti-depressants, antibiotics, anxiolytics.
2. When tolerance develops, doctors have to find new ways to effectively manage symptoms.
Risks from developing tolerance can include: relapse or flare-up of a condition, need for
higher doses, addiction, unintentional medication errors.
3. Tolerance can develop to many classes of medications and is a normal reaction. In some
cases, your doctor might slowly stop the medication and restart it after a break, depending on
the condition. This gives your body a chance to reset. It doesn’t always work long term but
can be one option to try.
4. Developing tolerance means your doctor will need to reevaluate your treatment. This can
be challenging sometimes, because increasing the dose might mean more side effects. It might
be harder to find other medications that work. For other, unregulated drugs, there are more
risks of overdose and other complications.

3. Tell whether the following statements are true or false according to the texts. Correct
those that are false.

1. The drug tolerance definition refers to the body’s ability governed by genetic factors
and adaptive changes by the body and it includes various symptoms. T/F
2. Drug tolerance should be confused with drug tolerability, as it refers to the degree to
which overt adverse effects of a drug can be tolerated by a patient. T/F
3. Physiological tolerance never occurs when an organism builds up a resistance to the
effects of a substance after repeated exposure. T/F
4. Tolerance refers to the process by which the body acclimates to the absence of an
abused drug. T/F
5. Drug tolerance is a pharmacological concept describing subjects' reduced reaction to a
drug following its repeated use. T/F

4. Make up 5 special questions in order to point out the key points that should be
emphasized concerning the text „Drug Tolerance”.
5. In your group read one of the following passages to learn more about Gastrointestinal
drugs. Insert the words and phrases into the correct place in your text. Analyze the
obtained information with the other group.
Pharmacodynamic tolerance begins when the cellular response to a ____________is reduced
with repeated use. A common cause of pharmacodynamic ___________is high concentrations
of a substance constantly binding with the receptor, desensitizing it through
constant__________. Other possibilities include a reduction in receptor density, or other
mechanisms leading to changes in action __________firing rate. Pharmacodynamic tolerance
to a receptor antagonist involves the reverse, i.e., ___________receptor firing rate, an increase
in receptor density, or other mechanisms. While most occurrences of pharmacodynamic
tolerance occur after sustained ____________to a drug, instances of acute or instant tolerance
can occur. Pharmacokinetic tolerance (dispositional tolerance) occurs because of a
decreased___________ of the substance reaching the site it affects. This may be caused by an
increase in induction of the enzymes required for ___________of the drug. This type of
tolerance is most evident with oral ingestion, because other routes of drug administration
bypass first-pass ___________. Enzyme induction is partly responsible for the _________of
tolerance, in which repeated use of a drug leads to a reduction of the drug's effect.

Substance, exposure, tolerance, metabolism, phenomenon, quantity, interaction,

degradation, increased, potential.

Behavioral tolerance occurs with the use of certain psychoactive drugs, where tolerance to a
__________ effect of a drug, such as increased motor activity by methamphetamine, occurs
with repeated use. It may occur through drug-independent __________or as a form of
pharmacodynamic tolerance in the brain; the former mechanism of behavioral tolerance
occurs when one learns how to actively __________drug-induced impairment through
practice. Behavioral tolerance is often context-dependent, meaning tolerance depends on the
___________in which the drug is administered, and not on the drug itself. Behavioral
sensitization describes the opposite___________. By the time tolerance has developed, the
addict has likely experienced the symptoms of other disorders; which essentially means that
the person’s ___________is now compromised by competing disorders. This is clinically
significant because it will shape the nature of the treatment___________. Occurring
simultaneously with tolerance is another physical phenomenon, dependence which emerges
alongside tolerance and is the ___________by which body requires increasingly larger
_________to experience the same results one initially experienced before_________ set in. In
this regard, the two phenomena are not only bound to one another but predictable hallmarks
of addictive__________.

Behavioral, environment, learning, tolerance, overcome, doses, administered, phenomenon,

psychology, process, pathology.

9. Project work. Make a presentation on Drug Tolerance. Be ready to present it to your

colleagues.
LISTENING

Drug Tolerance meaning and explanation. https://www.youtube.com/watch?v=_9TnRoEkXiE

1. Watch the video. Underline the right variant

A common cause/source of pharmacodynamic tolerance is high concentrations of a substance

constantly binding with the receptor decensitising through constant interaction/direction.
Other possibilities include a reduction/deduction in receptor density usually associated with
receptor/detector agonists or other mechanisms leading to changes in action potential firing
date/rate. Pharmacodynamic tolerance occurs after maintained/sustained exposure to a drug
instances of acute or instant tolerance tachyphylaxis can occur. Pharmacokinetics
differs/refers to the absorption, distribution, metabolism and excretion of drugs. All
psychoactive drugs are first absorbed into the bloodstream, carried/varied to various parts of
the body including the site of action distribution broken down in some fashion metabolism
and ultimately removed from the body. All of these factors are very/merry important
determinants of crucial pharmacological properties of a drug its potency side-effects and
duration of action. Pharmacokinetic tolerance, dispositional tolerance occur because of a
decreased/increased quantity of the substance reaching/reechy the cited effects. Behavioral
tolerance occurs with the use of certain psychoactive drugs being often context dependent i.e.
on the environment in wich drug is edministered and not on the drug itself. Behavioral
sensitization describes/prescribes the opposite phenomenon.

2. Answer the questions

1. What is drug tolerance?

2. What factors does drug tolerance involve?
3. What is drug desensitisation?
4. What is the reverse concept to drug tolerance?
5. What may tolerance lead to?

3. Tell whether the following statements are true or false according to the texts. Correct
those that are false.
 1. Heavy drinkers initially develop tolerance to alcohol requiring to drink larger amounts
to achieve a similar effect.
2. Excessive drinking can cause liver damage which can lead to intoxication when
drinking even small amounts of alcohol.
3. Drug tolerance should not be confused with drug tolerability, which refers to the
degree to which overt effects of a drug can be tolerated by a patient.
4. Tachyphylaxis is a subcategory of drug tolerance referring to cases of sudden short
term onset of telerance following the administration of a drug.
5. Pharmacodynamic tolerance begins when the cellular response to a substance is
reduced with repeated use.

References
https://www.healthline.com/health/drug-tolerance
https://www.articlecity.com/blog/drug-tolerance-definition-psychology/
https://en.wikipedia.org/wiki/Drug_tolerance
https://www.youtube.com/watch?v=_9TnRoEkXiE